An increase in inflammatory cytokines, chemokines and acute phase mediators have been associated with a number of neuroinflammatory and neurological disorders including multiple sclerosis, trauma, stroke, AIDS dementia, tumor progression and Alzheimer?s Disease (AD). The hallmark pathological feature of AD is the accumulation of b-amyloid (Ab) plaques, the ensuing neurodegeneration and neuroinflammation within the brains of AD patients. The molecular mechanisms underlying the onset and progression of Alzheimer?s disease and the possible role of the immune system are not well understood. To address this issue, we have utilized custom-made microarrays, which contain a high number of immune-related cDNA clones, to determine if we could isolate Alzheimer?s disease (AD)-specific changes in gene expression, as compared to patients suffering from other forms of dementia, such as Parkinson?s dementia (PD), hippocampal sclerosis (HS), or dementia that lacked any distinct histology (DLDH) and non-demented age-matched controls. RNA was isolated from fresh frozen inferior parietal lobes (IPL) slices from 6 AD patients, 6 PD or DLDH patients and 6 age-matched controls. The AD samples were also matched for similar numbers of plaques and tangles, indicating a similar state of neurodegeneration. RNA was reverse-transcribed in the presence of 33P-dCTP and hybridized to the arrays. By sampling across a given slice of tissue, gene expression profiles reflecting the differences between patients suffering from AD or non-AD dementia and controls were obtained. Spot densities obtained from the scanned filters were subjected to a Z-transformation, and both distance-based gene selection analysis and hierarchical clustering was performed. We find that non-AD dementia exhibits a very distinct gene expression profile than AD or age-matched control subjects. Patients suffering from AD are more similar to the non-demented controls, but also express a very distinct cohort of AD-specific genes. Several genes associated with immune cell activation and cytokine generation were also found in these analyses. Several of these genes were validated using both real time PCR and immunohistochemistry. Studies are underway to elucidate the role of these genes in AD pathology. Overall, we believe there are both common and distinct biochemical and molecular mechanisms involved in both acute and chronic neurodegenerative and neuroinflammatory processes. Understanding the commonality between these various pathways may provide valuable information into the diagnosis and control of these disease states.